Comparison between two surgical techniques for prenatal correction of meningomyelocele in sheep

OBJECTIVE: To compare the classical neurosurgical technique with a new simplified technique for prenatal repair of a myelomeningocelelike defect in sheep. METHODS: A myelomeningocele-like defect (laminectomy and dural excision) was created in the lumbar region on day 90 of gestation in 9 pregnant sheep. Correction technique was randomized. In Group 1 the defect was corrected using the classic neurosurgical technique of three-layer suture (dura mater, muscle and skin closure) performed by a neurosurgeon. In Group 2, a fetal medicine specialist used a biosynthetic cellulose patch to protect the spinal cord and only the skin was sutured above it. Near term (day 132 of gestation) fetuses were sacrificed for pathological analysis. RESULTS: There were two miscarriages and one maternal death. In total, six cases were available for pathological analysis, three in each group. In Group 1, there were adherence of the spinal cord to the scar (meningo-neural adhesion) and spinal cord architecture loss with posterior funiculus destruction and no visualization of grey matter. In Group 2, we observed in all cases formation of a neo-dura mater, separating the nervous tissue from adjacent muscles, and preserving the posterior funiculus and grey matter. CONCLUSION: The new simplified technique was better than the classic neurosurgical technique. It preserved the nervous tissue and prevented the adherence of the spinal cord to the scar. This suggests the current technique used for the correction of spina bifida in humans may need to be reassessed.

Sustained attention in children with two etiologies of early hydrocephalus.

Several studies have shown that children with spina bifida meningomyelocele (SBM) and hydrocephalus have attention problems on parent ratings and difficulties in stimulus orienting associated with a posterior brain attention system. Less is known about response control and inhibition associated with an anterior brain attention system. Using the Gordon Vigilance Task (Gordon, 1983), we studied error rate, reaction time, and performance over time for sustained attention, a key anterior attention function, in 101 children with SBM, 17 with aqueductal stenosis (AS; another condition involving congenital hydrocephalus), and 40 typically developing controls (NC). In SBM, we investigated the relation between cognitive attention and parent ratings of inattention and hyperactivity and explored the impact of medical variables. Children with SBM did not differ from AS or NC groups on measures of sustained attention, but they committed more errors and responded more slowly. Approximately one-third of the SBM group had attention symptoms, although parent attention ratings were not associated with task performance. Hydrocephalus does not account for the attention profile of children with SBM, which also reflects the distinctive brain dysmorphologies associated with this condition.

Verb generation in children with spina bifida.

We investigated verb generation in children with spina bifida meningomyelocele (SBM; n = 55) and in typically developing controls (n = 32). Participants completed 6 blocks (40 trials each) of a task requiring them to produce a semantically related verb in response to a target noun and an additional 40 trials on which they were simply required to read target nouns aloud. After controlling for reading response time, groups did not differ significantly in verb generation response time or learning. Children with SBM produced more non-verb errors than controls and tended to repeat their mistakes over blocks. Verb generation performance was associated with brain volume measures in participants with SBM. Congenital cerebellar dysmorphology is associated with impaired performance in verb generation accuracy, although not with increased response times to produce verbs

Strong-meter and weak-meter rhythm identification in spina bifida meningomyelocele and volumetric parcellation of rhythm-relevant cerebellar regions.

Children with spina bifida meningomyelocele (SBM) are impaired relative to controls in terms of discriminating strong-meter and weak-meter rhythms, so congenital cerebellar dysmorphologies that affect rhythmic movements also disrupt rhythm perception. Cerebellar parcellations in children with SBM showed an abnormal configuration of volume fractions in cerebellar regions important for rhythm function: a smaller inferior-posterior lobe, and larger anterior and superior-posterior lobes.

Characteristics of a spina bifida population including North American Caucasian and Hispanic individuals.

BACKGROUND: Meningomyelocele (MM) is a common human birth defect. MM is a disorder of neural development caused by contributions from genes and environmental factors that result in the NTD and lead to a spectrum of physical and neurocognitive phenotypes. METHODS: A multidisciplinary approach has been taken to develop a comprehensive understanding of MM through collaborative efforts from investigators specializing in genetics, development, brain imaging, and neurocognitive outcome. Patients have been recruited from five different sites: Houston and the Texas-Mexico border area; Toronto, Canada; Los Angeles, California; and Lexington, Kentucky. Genetic risk factors for MM have been assessed by genotyping and association testing using the transmission disequilibrium test. RESULTS: A total of 509 affected child/parent trios and 309 affected child/parent duos have been enrolled to date for genetic association studies. Subsets of the patients have also been enrolled for studies assessing development, brain imaging, and neurocognitive outcomes. The study recruited two major ethnic groups, with 45.9% Hispanics of Mexican descent and 36.2% North American Caucasians of European descent. The remaining patients are African-American, South and Central American, Native American, and Asian. Studies of this group of patients have already discovered distinct corpus callosum morphology and neurocognitive deficits that associate with MM. We have identified maternal MTHFR 667T allele as a risk factor for MM. In addition, we also found that several genes for glucose transport and metabolism are potential risk factors for MM. CONCLUSIONS: The enrolled patient population provides a valuable resource for elucidating the disease characteristics and mechanisms for MM development.

Genes in glucose metabolism and association with spina bifida.

The authors test single nucleotide polymorphisms (SNPs) in coding sequences of 12 candidate genes involved in glucose metabolism and obesity for associations with spina bifida. Genotyping was performed on 507 children with spina bifida and their parents plus anonymous control DNAs from Hispanic and Caucasian individuals. The transmission disequilibrium test was performed to test for genetic associations between transmission of alleles and spina bifida in the offspring (P < .05). A statistically significant association between Lys481 of HK1 (G allele), Arg109Lys of LEPR (G allele), and Pro196 of GLUT1 (A allele) was found ( P = .019, .039, and .040, respectively). Three SNPs on 3 genes involved with glucose metabolism and obesity may be associated with increased susceptibility to spina bifida.

i-Cobb - An innovative technique in spinal radiographic measurement

The measurement of Cobb angles from radiographs is routine practice in spinal clinics. The technique relies on the use and availability of specialist equipment such as a goniometer, cobbometer or protractor. The aim of this study was to validate the use of i-Phone (Apple Inc) combined with Tilt Meter Pro software as compared to a protractor in the measurement of Cobb angles. Between November 2008 and December 2008 20 patients were selected at random from the Paediatric Spine Research Groups Database. A power calculation was performed which indicated if n=240 measurements the study had a 96% chance of detecting a 5 degree difference between groups. All patients had idiopathic scoliosis with a range of curve types and severities. The study found the i-Phone combined with Tilt Meter Pro software offers a faster alternative to the traditional method of Cobb angle measurement. The use of i-Phone offers a more convenient way of measuring Cobb angles in the outpatient setting. The intra-observer repeatability of the iPhone is equivalent to the protractor in the measurement of Cobb angles.

I-cobb - An innovative technique in spinal radiographic measurement

The measurement of Cobb angles on radiographs of patients with spinal deformities is routine practice in spinal clinics. The technique relies on the use and availability of specialist equipment such as a goniometer, cobbometer or protractor. The aim of this study was to validate the use of i-Phone (Apple Inc) combined with Tilt Meter Pro software as compared to a protractor in the measurement of Cobb angles. The i-Phone combined with Tilt Meter Pro software offers a faster alternative to the traditional method of Cobb angle measurement. The use of i-Phone offers a more convenient way of measuring Cobb angles in the outpatient setting. The intra-observer repeatability of the iPhone is equivalent to the protractor in the measurement of Cobb angles.

Reduction of Secondary Degeneration after Spinal Cord Injury by Acute Delivery of Proinflammatory Growth Factors

INTRODUCTION Inflammation is a protective attempt to facilitate the removal of damaged tissue and to initiate the healing response in other tissues. However, after spinal cord injury (SCI), this response is prolonged leading to secondary degeneration and glial scarring. Here, we investigate the potential of sustained delivery of pro-inflammatory factors vascular endothelial growth factor (VEGF) and platelet derived growth factor (PDGF) to increase early inflammatory events and promote inflammatory resolution. Method Animal ethics approval was obtained from the Queensland University of Technology. Adult Wistar-Kyoto rats (12-16 weeks old) were subjected to laminectomies and T10 hemisections. Animals were then randomised to treatment (implantation of osmotic pump (Alzet) loaded with 5ug VEGF & 5 ug PDGF) or control groups (lesion control or lesion plus pump delivering PBS). Rats were sacrificed at one month and the spinal cords were harvested and examined by immunohistology, using anti-neurofilament-200(NF200) and anti- ionized calcium binding adapter molecule 1 (Iba1). One way ANOVA was used for statistic analysis. Results At 1 month, active pump-treated cords showed a high level of axonal filament throughout the defects as compared to the control groups. The mean lesion size, as measured by NF200, was 0.47mm2 for the lesion control, 0.39mm2 for the vehicle control and 0.078mm2 for the active pump group. Significant differences were detected between the active pump group and the two control groups (AP vs LC p= 0.017 AG vs VC p= 0.004). Iba-1 staining also showed significant differences in the post-injury inflammatory response. Discussion We have shown that axons and activated microglia are co-located in the lesion of the treated cord. We hypothesise the delivery of VEGF/PDGF increases the local vessel permeability to inflammatory cells and activates these along with the resident microglia to threshold population, which ultimately resolved the prolonged inflammation. Here, we have shown that maintaining the inflammatory signals for at least 7 days improved the morphology of the injured cord. Conclusion This study has shown that boosting inflammation, by delivery VEGF/PDGF, in the early phase of SCI helps to reduce secondary degeneration and may promote inflammation resolution. This treatment may provide a platform for other neuro-regenrative therapies.

Biological performance of a polycaprolactone-based scaffold used as fusion cage device in a large animal model of spinal reconstructive surgery

A bioactive and bioresorbable scaffold fabricated from medical grade poly (epsilon-caprolactone) and incorporating 20% beta-tricalcium phosphate (mPCL–TCP) was recently developed for bone regeneration at load bearing sites. In the present study, we aimed to evaluate bone ingrowth into mPCL–TCP in a large animal model of lumbar interbody fusion. Six pigs underwent a 2-level (L3/4; L5/6) anterior lumbar interbody fusion (ALIF) implanted with mPCL–TCP þ 0.6 mg rhBMP-2 as treatment group while four other pigs implanted with autogenous bone graft served as control. Computed tomographic scanning and histology revealed complete defect bridging in all (100%) specimen from the treatment group as early as 3 months. Histological evidence of continuing bone remodeling and maturation was observed at 6 months. In the control group, only partial bridging was observed at 3 months and only 50% of segments in this group showed complete defect bridging at 6 months. Furthermore, 25% of segments in the control group showed evidence of graft fracture, resorption and pseudoarthrosis. In contrast, no evidence of graft fractures, pseudoarthrosis or foreign body reaction was observed in the treatment group. These results reveal that mPCL–TCP scaffolds could act as bone graft substitutes by providing a suitable environment for bone regeneration in a dynamic load bearing setting such as in a porcine model of interbody spine fusion.

Development of a computer simulation tool for application in adolescent spinal deformity surgery

Scoliosis is a three-dimensional spinal deformity which requires surgical correction in progressive cases. In order to optimize correction and avoid complications following scoliosis surgery, patient-specific finite element models (FEM) are being developed and validated by our group. In this paper, the modeling methodology is described and two clinically relevant load cases are simulated for a single patient. Firstly, a pre-operative patient flexibility assessment, the fulcrum bending radiograph, is simulated to assess the model's ability to represent spine flexibility. Secondly, intra-operative forces during single rod anterior correction are simulated. Clinically, the patient had an initial Cobb angle of 44 degrees, which reduced to 26 degrees during fulcrum bending. Surgically, the coronal deformity corrected to 14 degrees. The simulated initial Cobb angle was 40 degrees, which reduced to 23 degrees following the fulcrum bending load case. The simulated surgical procedure corrected the coronal deformity to 14 degrees. The computed results for the patient-specific FEM are within the accepted clinical Cobb measuring error of 5 degrees, suggested that this modeling methodology is capable of capturing the biomechanical behaviour of a scoliotic human spine during anterior corrective surgery.

Secondary curve behaviour in Lenke IC class adolescent idiopathic scoliosis following video assisted thoracoscopic spinal fusion

Introduction. Ideally after selective thoracic fusion for Lenke Class IC (i.e. major thoracic / secondary lumbar) curves, the lumbar spine will spontaneously accommodate to the corrected position of the thoracic curve, thereby achieving a balanced spine, avoiding the need for fusion of lumbar spinal segments1. The purpose of this study was to evaluate the behaviour of the lumbar curve in Lenke IC class adolescent idiopathic scoliosis (AIS) following video-assisted thoracoscopic spinal fusion and instrumentation (VATS) of the major thoracic curve. Methods. A retrospective review of 22 consecutive patients with AIS who underwent VATS by a single surgeon was conducted. The results were compared to published literature examining the behaviour of the secondary lumbar curve where other surgical approaches were employed. Results. Twenty-two patients (all female) with AIS underwent VATS. All major thoracic curves were right convex. The average age at surgery was 14 years (range 10 to 22 years). On average 6.7 levels (6 to 8) were instrumented. The mean follow-up was 25.1 months (6 to 36). The pre-operative major thoracic Cobb angle mean was 53.8° (40° to 75°). The pre-operative secondary lumbar Cobb angle mean was 43.9° (34° to 55°). On bending radiographs, the secondary curve corrected to 11.3° (0° to 35°). The rib hump mean measurement was 15.0° (7° to 21°). At latest follow-up the major thoracic Cobb angle measured on average 27.2° (20° to 41°) (p<0.001 – univariate ANOVA) and the mean secondary lumbar curve was 27.3° (15° to 42°) (p<0.001). This represented an uninstrumented secondary curve correction factor of 37.8%. The mean rib hump measured was 6.5° (2° to 15°) (p<0.001). The results above were comparable to published series when open surgery was performed. Discussion. VATS is an effective method of correcting major thoracic curves with secondary lumbar curves. The behaviour of the secondary lumbar curve is consistent with published series when open surgery, both anterior and posterior, is performed.

Computed tomography analysis of sagittal plane parameters in adolescent idiopathic scoliosis treated by video assisted thoracoscopic spinal fusion and instrumentation

One of the primary treatment goals of adolescent idiopathic scoliosis (AIS) surgery is to achieve maximum coronal plane correction while maintaining coronal balance. However maintaining or restoring sagittal plane spinal curvature has become increasingly important in maintaining the long-term health of the spine. Patients with AIS are characterised by pre-operative thoracic hypokyphosis, and it is generally agreed that operative treatment of thoracic idiopathic scoliosis should aim to restore thoracic kyphosis to normal values while maintaining lumbar lordosis and good overall sagittal balance. The aim of this study was to evaluate CT sagittal plane parameters, with particular emphasis on thoracolumbar junctional alignment, in patients with AIS who underwent Video Assisted Thoracoscopic Spinal Fusion and Instrumentation (VATS). This study concluded that video-assisted thoracoscopic spinal fusion and instrumentation reliably increases thoracic kyphosis while preserving junctional alignment and lumbar lordosis in thoracic AIS.

Design and evaluation of an MRI compatible axial compression device for 3D assessment of spinal deformity and flexibility

Magnetic Resonance Imaging (MRI) offers a valuable research tool for the assessment of 3D spinal deformity in AIS, however the horizontal patient position imposed by conventional scanners removes the axial compressive loading on the spine which is an important determinant of deformity shape and magnitude in standing scoliosis patients. The objective of this study was to design, construct and test an MRI compatible compression device for research into the effect of axial loading on spinal deformity using supine MRI scans. The compression device was designed and constructed, consisting of a vest worn by the patient, which was attached via straps to a pneumatically actuated footplate. An applied load of 0.5 x bodyweight was remotely controlled by a unit in the scanner operator’s console. The entire device was constructed using non-metallic components for MRI compatibility. The device was evaluated by performing unloaded and loaded supine MRI scans on a series of 10 AIS patients. The study concluded that an MRI compatible compression device had been successfully designed and constructed, providing a research tool for studies into the effect of axial loading on 3D spinal deformity in scoliosis. The 3D axially loaded MR imaging capability developed in this study will allow future research investigations of the effect of axial loading on spinal rotation, and for imaging the response of scoliotic spinal tissues to axial loading.